Method for ablating tissue to facilitate implantation and apparatus and kit for use therewith

ABSTRACT

A method for treating a mammalian body having tissue comprising creating a cavity in the tissue formed by an internal surface of the tissue. The internal surface is ablated. An implant-forming material is introduced into the cavity to create an implant in the tissue. The ablation of the internal surface inhibits migration of the implant. An apparatus and kit for use with the method are provided.

CROSS-REFERENCE TO RELATED APPLICATION

The application claims priority to U.S. provisional patent applicationNo. 60/959,441 filed on Jul. 13, 2007, the entire content of which isincorporated herein by this reference.

SCOPE OF THE INVENTION

The present invention relates to methods and devices for treating amammalian body and more particularly to methods and devices for creatingimplants in tissue of a mammalian body.

BACKGROUND

Medical devices have been provided for the delivery of a material tovarious portions of a wall forming a vessel such as the gastrointestinaltract of a mammalian body to create implants in the wall. See, forexample, U.S. Pat. No. 6,251,063. There remains, however, a need forinhibiting migration of such implants in the wall.

SUMMARY OF THE INVENTION

A method for treating a mammalian body having tissue comprising creatinga cavity in the tissue formed by an internal surface of the tissue isprovided. The internal surface is ablated. An implant-forming materialis introduced into the cavity to create an implant in the tissue. Theablation of the internal surface inhibits migration of the implant. Anapparatus and kit for use with the method are provided.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are somewhat schematic in someinstances and are incorporated in and form a part of this specification,illustrate several embodiments of the invention and, together with thedescription, serve to explain the principles of the invention.

FIG. 1 is a plan view of a medical device having an apparatus forablating tissue of the present invention for use in the method of thepresent invention.

FIG. 2 is a side view, partially cut away, of the distal extremity ofthe apparatus for ablating tissue of FIG. 1 taken along the line 2-2 ofFIG. 1.

FIG. 3 is a plan view of the medical device of FIG. 1 having animplant-forming apparatus for use in the method of the presentinvention.

FIG. 4 is a side view, partially cut away, of the distal extremity ofthe implant-forming apparatus of FIG. 3 taken along the line 4-4 of FIG.3.

FIG. 5 is a plan view of a kit, somewhat schematic and partially cutaway, for treating the upper portion of the gastrointestinal tract inaccordance with the method of the present invention.

FIG. 6 is an elevational view of a portion of the medical device of FIG.1 in a passageway of a mammalian body.

FIG. 7 is an enlarged view of a portion of the medical device of FIG. 1in a passageway of a mammalian body.

FIG. 8 is an enlarged view of the distal extremity of the apparatus forablating tissue of FIG. 1 penetrating tissue in a passageway of amammalian body.

FIG. 9 is an enlarged view of the distal extremity of the apparatus forablating tissue of FIG. 1 dissecting tissue in a passageway of amammalian body.

FIG. 10 is an enlarged view of the distal extremity of the apparatus forablating tissue of FIG. 1 ablating tissue in a passageway of a mammalianbody.

FIG. 11 is an enlarged view of the distal extremity of theimplant-forming apparatus of FIG. 3 penetrating a cavity in tissue of apassageway of a mammalian body.

FIG. 12 is a cross-sectional view of an implant formed by the method ofthe present invention in tissue of a passageway of a mammalian.

FIG. 13 is a side view, similar to FIG. 2, of another embodiment of thedistal extremity of the apparatus for ablating tissue of the presentinvention.

FIG. 14 is a cross-sectional view of the apparatus for ablating tissueof FIG. 13 taken along the line 14-14 of FIG. 13.

FIG. 15 is a side view, similar to FIG. 2 and partially cut away, of afurther embodiment of the distal extremity of the apparatus for ablatingtissue of the present invention.

FIG. 16 is a side view, similar to FIG. 2, of yet another embodiment ofthe distal extremity of the apparatus for ablating tissue of the presentinvention.

DESCRIPTION OF THE INVENTION

The method of the present invention can be performed with an apparatusor medical device of the type shown in FIGS. 1 and 3. The medical device21 of FIG. 1 includes a probe member or probe 22 having an opticalviewing device 23. A cavity-forming assembly or ablation apparatus 26 isslidably carried by probe 22. Treatment device 21 further includes aninflation fluid supply 27 coupled to the cavity-forming or ablationapparatus 26 and a radio frequency supply and controller 28 electricallycoupled to the ablation apparatus 26.

A conventional or other suitable gastroscope or endoscope can be usedfor probe or catheter 22. An exemplary probe 22 includes a flexibleelongate tubular member or insertion tube 31 having proximal and distalextremities 31 a and 31 b and a distal face 32. Insertion tube 31 hasbeen sectioned in FIG. 1 so that only a portion of proximal extremity 31a and distal extremity 31 b are shown. A handle means or assembly iscoupled to proximal extremity 31 a of the insertion tube 31 and includesa conventional handle 33. The tubular insertion tube 31 is provided withat least one bore and preferably a plurality of bores or passageways 36extending from proximal extremity 31 a to distal extremity 31 b. Aportion of one such passageway 36 is shown in dashed lines in FIG. 1.

Optical viewing device 23 is formed integral with probe 22 and has anoptical element or objective lens (not shown) carried by one of thepassageways 36 of the device 23. The objective lens has a field of viewat distal face 32 which permits the operator to view forwardly ofinsertion tube distal extremity 31 b. Optical viewing device 23 furtherincludes an eye piece 41 mounted on the proximal end of handle 33. Aconnection cable 42, a portion of which is shown in FIG. 1, extends fromhandle 33 to a conventional light source 43. At least one light guideextends through cable 42 and insertion tube 31 for providingillumination forwardly of distal face 32 of the insertion tube 31.

One of the passageways 36 provided in insertion tube 31 extends to aside port 46 formed in handle 33. Ablation apparatus 26 can be slidablyintroduced into such passageway 36 by means of side port 46. Insertiontube 31 is flexible so as to facilitate its insertion and advancementthrough a body and is provided with a bendable distal end forselectively directing distal face 32 in a desired direction. A pluralityof finger operable controls 47 are provided on handle 33 for, amongother things, operating the bendable distal end of insertion tube 31 andthe supply and removal of fluids through the insertion tube 31.

Ablation apparatus 26 includes an elongate member 51 made from anysuitable material such as plastic and more specifically a thermoplasticsuch as but not limited to polypropylene, polyethylene or nylon and morepreferably polypropylene. The elongate member 51 has a proximal endportion or extremity 51 a and a distal end portion or extremity 51 b(see FIGS. 1 and 2). The elongate member preferably has a rounded end 52at the distal extremity, as shown in FIG. 2, for facilitating bluntdissection of tissue. The ablation apparatus 26 further includes atissue-dissecting or cavity-forming device 53 disposed on the distalextremity of the elongate member. Such device 53, also referred toherein as an inflatable device, preferably includes a balloon 54 andmore preferably a perforated or “weeping” balloon, such as of the typedescribed in U.S. Pat. No. 6,673,290, the entire content of which isincorporated herein by this reference. Balloon or dissecting element 54has an expandable-collapsible body 56 made from any suitable materialsuch as thermoplastic or any of the materials such as polyurethanedisclosed in the table set forth below taken from Table 6 of U.S. Pat.No. 6,475,213, the entire content of which is incorporated herein bythis reference.

Summary of Porous Ablation Materials Bubble Point No Flow ImpedanceMat'l Lesion Mat'l Mfgr. HPhb HPhl Pore Size Value Impedance w/FlowBrkdwn Depth Dialysis Spectrum X .025 μm High 87 Ω 87 Ω No 13.3 mmTubing Nylon Spectrum X 5 μm Med 68 Ω 69 Ω No 9.9 mm Mesh Stain-StSpectrum 30 μm Low 67 Ω 67 Ω No 9.7 mm Mesh Polycarb Millipore X 1.2 μmHigh 78 Ω 78 Ω No 11.6 mm Film 14 psi Polyether- Gelman X 5 μm Med 80 Ω80 Ω No 10.6 mm sulfone 1-6 psi Modified Gelman X 10 μm Med 68 Ω 68 ΩYes 9.9 mm Acrylic 1-6 psi copolymer Modified Gelman X 5 μm High >300 Ω 70 Ω Yes 11.0 mm w/flow Acrylic copolymer Modified Gelman X 10 μmHigh >300 Ω  61 Ω Yes 11.3 mm w/flow Acrylic w/ Backing

The foregoing table demonstrates that pore sizes may be decreased usinghydrophilic materials, thereby minimizing or stopping liquid perfusionthrough the porous material, while till enabling ionic transport throughthe membrane. Hydrophobic porous materials make possible the realizationof high resistivity porous electrodes. On the other hand, hydrophilicporous materials make possible the realization of low resistivity porouselectrodes.

Body 56 is preferably tubular in conformation and has annular proximaland distal end portions 56 a, 56 b which are adhered or otherwisesecured to distal extremity 51 b of the elongate member 51 inlongitudinally spaced apart positions by any suitable means such as anadhesive (not shown). The balloon 54 has an hollow interior or space 57consisting of the annular spaced provided between the balloon body 56and the elongate member 51. Balloon 54, that is the expandable portionof the balloon, has a length ranging from one to twenty millimeters andpreferably ten millimeters and a width ranging from one to thirtymillimeters and preferably five millimeters. The ablation apparatus 26has a length so that when balloon 54 extends distally beyond face 32 ofthe insertion tube 31, proximal extremity 51 a of the elongate member 51is accessible at side port 46.

The elongate member 51 has at least a first lumen 68, and preferably asecond lumen 59, extending longitudinally from the proximal extremity 51a to the distal extremity 51 b of the elongate member (see FIG. 2). Thefirst and second lumens 58 and 59 each opens into the hollow interior 57of the expandable-collapsible body 56 at the distal extremity of theelongate member and is fluidly coupled to the inflation fluid supply 27connected to the proximal extremity of the elongate member. First lumen58 serves as an inflation lumen, and optional second lumen 59 serves asa return lumen when circulation of fluid is desired through balloon 54.Although any suitable fluid may be provided within supply 27, aconductive fluid is preferred and a saline solution is more particularlypreferred. A finger-grippable element 71 is coupled to the proximalextremity of the elongate member 51 and includes at least one suitablefitting 72 for coupling the first lumen 58 to fluid supply 27 so as topermit fluid communication between supply 27 and inflation lumen 58. Anoptional pressure monitor 61 and an optional pump 62 can be fluidlycoupled to the inlet line 63 from supply 27 to fitting 72, asillustrated in FIG. 1. A second suitable fitting 72 can be provided onelement 71 when optional return lumen 59 is included in ablationapparatus 26. A return or outlet line 64 from such fitting, not shown inFIG. 1, is shown schematically as a dashed line from finger-grippableelement 71 in FIG. 1.

Ablation apparatus 26 further includes at least one ablation element 73provided on the distal extremity 51 b of the elongate member 51. Theexpandable-collapsible body 56 is partially cut away in FIG. 2 to revealan annular electrode 74 disposed within the interior 57 of the balloon54 which is part of the ablation element 73. The active electrode 74 iselectrically coupled to the radio frequency supply or generator 28 by,for example, a conductive wire or lead 75 (shown as a dashed line inFIG. 2) extending from the active electrode through the elongate member51 to a connector 76 provided on grippable element 71 at the proximalextremity 51 a of the elongate member 51. An electrical cable 77 isremovably securable to the connector 76 and extends from the connector76 to the radio frequency generator 28 (shown schematically in FIG. 1).When ablation element 73 is utilized in a monopolar mode, an indifferentor return electrode 78 is electrically coupled to generator andcontroller 28 and utilized. The indifferent or return electrode 78 isshown schematically in FIG. 1 and can be in the form of a ground pad.

A plurality of apertures or pores 79, some of which are shown in FIG. 2,extend through body 56 in spaced-apart positions for permitting ionictransport between the hollow interior of the expandable-collapsible body56 and the exterior of the balloon 54, more specifically flow of theconductive fluid within the balloon to the exterior of the balloon.Although the diameter and spacing of pores 79 can be as described inU.S. Pat. No. 6,475,213, it is preferred that the pores have a diameterranging from 0.025 to 30 microns, preferably five to 50 microns and morepreferably five to ten microns. The placement of the pores 79 and thesize of the pores 79 determine the porosity of the body 56. The porosityrepresents the space on the body 56 that does not contain material, oris empty, or is composed of pores 79. Expressed as a percentage,porosity represents the percent volume of the body 56 that is notoccupied by the body material. For materials having a porosity greaterthan about 10%, porosity P (in %) can be determined as follows:

P=100(1−ρ_(b)/ρ_(m))

where ρ_(b) is the density of the body 56 as determined by its weightand volume, and ρ_(m) is the density of the material from which the body56 is made. To derive porosity for materials having a porosity of lessthan about 10%, a scanning electron microscope can be used to obtain thenumber of pores and their average diameter. Porosity P (in %) is thenderived as follows:

P═Nπ(d ²/4)

where N is the pore density and equals (ρ_(n)/a), ρ_(n) is the number ofpores in the body 56, a is the total porous area of the body 56 (incentimeters²), π is the constant 3.1416 . . . , and d is the averagediameter of the pores (in centimeters). As such, weeping balloon 54 canbe considered part of the ablation element 73 of apparatus 26.

Elongate member 51 of ablation apparatus 26 can optionally include anadditional lumen 81 extending longitudinally from proximal extremity 51a to an opening 82 at distal extremity 51 b of the elongate member 51(see FIG. 2). A suitable tissue-incising element such as a guidewire 83is slidably disposed in lumen or passageway 81, as illustrated in FIGS.1 and 2. Guidewire 83 has a proximal extremity 83 a accessible from theproximal extremity 51 a of the elongate member, and having a grip 84secured thereto for facilitating hand-operable slidable movement of theguidewire 83 within passageway 81, and a distal extremity 83 b with asharpened or beveled tip 86 extendable from opening 82. The guidewirehas a diameter ranging from 0.014 to 0.018 inch.

Treatment device 21 includes an implant-forming apparatus which, afterremoval of ablation apparatus 26 from passageway 36 and side port 46 ofprobe 22, can be introduced through the side port 46 into the passageway36 as illustrated in FIG. 2. Such implant-forming apparatus can be inthe form of a needle assembly or injection device 96 similar to thatshown and described in U.S. Pat. No. 6,251,063, the entire content ofwhich is incorporated herein by this reference. More specifically,injection device 96 includes a stylet 97 having a needle member 98provided with a proximal end portion or extremity 98 a and a distal endportion or extremity 98 b and an optional sleeve member or sleeve 99provided with a proximal end portion or extremity 99 a and a distal endportion or extremity 99 b (see FIGS. 2 and 4). Sleeve or first tubularmember 99 is made from any suitable material such as flexible plastic ormetal and has a lumen 102 extending longitudinally therethrough forreceiving at least part of the needle member or second tubular member98. Although the sleeve 99 and the needle member 98 can be fixedrelative to each other, they are preferably slidable relative to eachother in a longitudinal direction. In this regard, needle member 98 isslidably disposed in sleeve 99 and movable between a retracted positionin which the needle member is recessed within distal end portion 99 b ofsleeve and an extended position in which the needle member 98 projectsdistally of the sleeve 99. Needle member 98 and sleeve 99 are slidablydisposed within passageway 36 and side port 49 of insertion tube 31 andeach have a length so that when distal end portions 98 b and 99 b areextending from distal extremity 31 b of the insertion tube 31 orotherwise in the vicinity of distal face 32, proximal end portions 98 aand 99 a are accessible at side port 46.

The hollow or tubular needle member 98 has a lumen or passage 103extending longitudinally therethrough from proximal end portion 98 a todistal end portion 98 b (see FIG. 4). In one preferred embodiment ofinjection device 26, the proximal end portion 98 a of the needle member98 and the central portion (not shown) of the needle member 98 are madefrom flexible plastic tubing and the distal extremity 98 b of the needlemember is a slender tube or needle 104 made from metal, rigid plastic orany other suitable material. Needle 104 is pressed into or otherwisesuitably attached to the distal end of such flexible plastic tubing ofthe needle member 98. Metal needle 104 is preferably made from stainlesssteel and has a size ranging from 14 to 30 gauge, preferably rangingfrom 23 to 26 gauge and more preferably approximately 23 gauge. Where a23 gauge needle 104 is provided, the internal diameter of needle bore orpassage 103 can range from 0.012 to 0.017 inch. Needle 104, as shown inFIG. 4, is preferably provided with a sharpened or beveled distal tip106.

A fluid connector 107 is secured or coupled to proximal end portion 98 aof needle member 98 and a gripping member or grip 108 is secured to theproximal end portion 99 a of the sleeve 99 (see FIG. 1). Fluid connector107 includes at least one luer fitting portion 111, or any othersuitable fitting portion, which communicates with the passageway 103 inneedle 98. Supply or reservoir 112 is coupled to the proximal extremityof injection device 26, and preferably to the proximal extremity 98 a ofneedle member 98, and can be of any suitable type. For example, one ormore syringes for containing an implantable or injectable material ofthe present invention, or the ingredients thereof, can be included insupply 112. The supply 112 is included within the means of medical ortreatment device 21 for introducing at least one liquid, solution,composition or material through passage 103 of needle 98 and out the atleast one distal opening provided in the distal extremity 98 b of needlemember 98.

When needle member 98 and sleeve 99 are not fixed relative to eachother, fluid connector 107 and grip 108 are movable longitudinallyrelative to each other so as to cause relative longitudinal movementbetween needle member 98 and sleeve 99. More specifically, grip 108 canbe slid forwardly and rearwardly on proximal end portion 98 a of theneedle 98 relative to fluid connector 107. Movement of grip 108forwardly relative to fluid connector 107 causes distal end portion 99 bof sleeve 99 to extend fully over distal end portion 98 b of the needlemember 98 so that the needle 104 is fully recessed within sleeve 99.Conversely, movement of grip 108 rearwardly relative to fluid connector107 causes sleeve distal end portion 99 b to retract relative to needledistal end portion 98 b so as to expose needle 104 distally of thesleeve 99.

Exemplary implantable materials or compositions which can be included insupply 112 and thus utilized in the method and apparatus of the presentinvention include any suitable material or composition from which animplant can be formed when a fluid, separately or in conjunction withanother fluid, is introduced into the tissue of a body. Theimplant-forming material hereof includes solutions. Although aqueous ornonaqueous solutions are among the fluids that can be used, an inert,nonresorbable material is preferred. Preferred nonaqueous solutions areany of the solutions disclosed in International Application No.PCT/US99/29427 filed Dec. 10, 1999, the entire content of which isincorporated herein by this reference. One such injectable orimplant-forming material comprises at least one solution which whenintroduced into the body forms a nonbiodegradable solid. As used herein,a solid means any substance that does not flow perceptibly undermoderate stress, has a definite capacity for resisting forces which tendto deform it (such as compression, tension and strain) and underordinary conditions retains a definite size and shape; such a solidincludes, without limitation, spongy and/or porous substances. One suchembodiment of the at least one solution is first and second solutionswhich when combined in the body form the nonbiodegradable solid. Anothersuch embodiment is a solution which can be introduced into the body as aliquid and from which a solid thereafter precipitates or otherwiseforms. A preferred embodiment of such a solution is a solution of abiocompatible composition and an optional biocompatible solvent whichcan further optionally include a contrast agent for facilitatingvisualization of the solution in the body. The solution can be aqueousor nonaqueous. Exemplary biocompatible compositions includebiocompatible prepolymers and biocompatible polymers.

A particularly preferred implant forming solution is a compositioncomprising from about 2.5 to about 8.0 weight percent of a biocompatiblepolymer, from about 52 to about 87.5 weight percent of a biocompatiblesolvent and optionally from about 10 to about 40 weight percent of abiocompatible contrast agent having a preferred average particle size ofabout 10 μm or less. It should be appreciated that any percents statedherein which include a contrast agent would be proportionally adjustedwhen the contrast agent is not utilized. Any contrast agent ispreferably a water insoluble biocompatible contrast agent. The weightpercent of the polymer, contrast agent and biocompatible solvent isbased on the total weight of the complete composition. In a preferredembodiment, the water insoluble, biocompatible contrast agent isselected from the group consisting of barium sulfate, tantalum powderand tantalum oxide. In still a further preferred embodiment, thebiocompatible solvent is dimethylsulfoxide (DMSO), ethanol, ethyllactate or acetone.

The term “biocompatible polymer” refers to polymers which, in theamounts employed, are non-toxic, chemically inert, and substantiallynon-immunogenic when used internally in the patient and which aresubstantially insoluble in physiologic liquids. Suitable biocompatiblepolymers include, by way of example, cellulose acetates (includingcellulose diacetate), ethylene vinyl alcohol copolymers, hydrogels(e.g., acrylics), poly(C1-C6) acrylates, acrylate copolymers, polyalkylalkacrylates wherein the alkyl and alk groups independently contain oneto six carbon atoms, polyacrylonitrile, polyvinylacetate, celluloseacetate butyrate, nitrocellulose, copolymers of urethane/carbonate,copolymers of styrene/maleic acid, and mixtures thereof. Copolymers ofurethane/carbonate include polycarbonates that are diol terminated whichare then reacted with a diisocyanate such as methylene bisphenyldiisocyanate to provide for the urethane/carbonate copolymers. Likewise,copolymers of styrene/maleic acid refer to copolymers having a ratio ofstyrene to maleic acid of from about 7:3 to about 3:7. Preferably, thebiocompatible polymer is also non-inflammatory when employed in situ.The particular biocompatible polymer employed is not critical and isselected relative to the viscosity of the resulting polymer solution,the solubility of the biocompatible polymer in the biocompatiblesolvent, and the like. Such factors are well within the skill of theart.

The polymers of polyacrylonitrile, polyvinylacetate, poly(C1-C6)acrylates, acrylate copolymers, polyalkyl alkacrylates wherein the alkyland alk groups independently contain one to six carbon atoms, celluloseacetate butyrate, nitrocellulose, copolymers of urethane/carbonate,copolymers of styrene/maleic acid and mixtures thereof typically willhave a molecular weight of at least about 50,000 and more preferablyfrom about 75,000 to about 300,000.

Preferred biocompatible polymers include cellulose diacetate andethylene vinyl alcohol copolymer. In one embodiment, the cellulosediacetate has an acetyl content of from about 31 to about 40 weightpercent. Cellulose diacetate polymers are either commercially availableor can be prepared by art recognized procedures. In a preferredembodiment, the number average molecular weight, as determined by gelpermeation chromatography, of the cellulose diacetate composition isfrom about 25,000 to about 100,000 more preferably from about 50,000 toabout 75,000 and still more preferably from about 58,000 to 64,000. Theweight average molecular weight of the cellulose diacetate composition,as determined by gel permeation chromatography, is preferably from about50,000 to 200,000 and more preferably from about 100,000 to about180,000. As is apparent to one skilled in the art, with all otherfactors being equal, cellulose diacetate polymers having a lowermolecular weight will impart a lower viscosity to the composition ascompared to higher molecular weight polymers. Accordingly, adjustment ofthe viscosity of the composition can be readily achieved by mereadjustment of the molecular weight of the polymer composition.

Ethylene vinyl alcohol copolymers comprise residues of both ethylene andvinyl alcohol monomers. Small amounts (e.g., less than 5 mole percent)of additional monomers can be included in the polymer structure orgrafted thereon provided such additional monomers do not alter theimplanting properties of the composition. Such additional monomersinclude, by way of example only, maleic anhydride, styrene, propylene,acrylic acid, vinyl acetate and the like.

Ethylene vinyl alcohol copolymers are either commercially available orcan be prepared by art recognized procedures. Preferably, the ethylenevinyl alcohol copolymer composition is selected such that a solution of8 weight-volume percent of the ethylene vinyl alcohol copolymer in DMSOhas a viscosity equal to or less than 60 centipoise at 20° C. and morepreferably 40 centipoise or less at 200C. As is apparent to one skilledin the art, with all other factors being equal, copolymers having alower molecular weight will impart a lower viscosity to the compositionas compared to higher molecular weight copolymers. Accordingly,adjustment of the viscosity of the composition as necessary for catheterdelivery can be readily achieved by mere adjustment of the molecularweight of the copolymer composition.

As is also apparent, the ratio of ethylene to vinyl alcohol in thecopolymer affects the overall hydrophobicity/hydrophilicity of thecomposition which, in turn, affects the relative watersolubility/insolubility of the composition as well as the rate ofprecipitation of the copolymer in an aqueous solution. In a particularlypreferred embodiment, the copolymers employed herein comprise a molepercent of ethylene of from about 25 to about 60 and a mole percent ofvinyl alcohol of from about 40 to about 75, more preferably a molepercent of ethylene of from about 40 to about 60 and a mole percent ofvinyl alcohol of from about 40 to about 60.

The term “contrast agent” refers to a biocompatible (non-toxic)radiopaque material capable of being monitored during injection into amammalian subject by, for example, radiography. The contrast agent canbe either water soluble or water insoluble. Examples of water solublecontrast agents include metrizamide, iopamidol, iothalamate sodium,iodomide sodium, and meglumine. The term “water insoluble contrastagent” refers to contrast agents which are insoluble in water (i.e., hasa water solubility of less than 0.01 milligrams per milliliter at 20°C.) and include tantalum, tantalum oxide and barium sulfate, each ofwhich is commercially available in the proper form for in vivo use andpreferably having a particle size of 10 μm or less. Other waterinsoluble contrast agents include gold, tungsten and platinum powders.Methods for preparing such water insoluble biocompatible contrast agentshaving an average particle size of about 10 μm or less are describedbelow. Preferably, the contrast agent is water insoluble (i.e., has awater solubility of less than 0.01 mg/ml at 20° C.)

The term “encapsulation” as used relative to the contrast agent beingencapsulated in the precipitate is not meant to infer any physicalentrapment of the contrast agent within the precipitate much as acapsule encapsulates a medicament. Rather, this term is used to meanthat an integral coherent precipitate forms which does not separate intoindividual components, for example into a copolymer component and acontrast agent component.

The term “biocompatible solvent” refers to an organic material liquid atleast at body temperature of the mammal in which the biocompatiblepolymer is soluble and, in the amounts used, is substantially non-toxic.Suitable biocompatible solvents include, by way of example,dimethylsulfoxide, analogues/homologues of dimethylsulfoxide, ethanol,ethyl lactate, acetone, and the like. Aqueous mixtures with thebiocompatible solvent can also be employed provided that the amount ofwater employed is sufficiently small that the dissolved polymerprecipitates upon injection into a human body. Preferably, thebiocompatible solvent is ethyl lactate or dimethylsulfoxide.

The compositions employed in the methods of this invention are preparedby conventional methods whereby each of the components is added and theresulting composition mixed together until the overall composition issubstantially homogeneous. For example, sufficient amounts of theselected polymer are added to the biocompatible solvent to achieve theeffective concentration for the complete composition. Preferably, thecomposition will comprise from about 2.5 to about 8.0 weight percent ofthe polymer based on the total weight of the composition and morepreferably from about 4 to about 5.2 weight percent. If necessary,gentle heating and stirring can be used to effect dissolution of thepolymer into the biocompatible solvent, e.g., 12 hours at 50° C.

Sufficient amounts of the contrast agent are then optionally added tothe biocompatible solvent to achieve the effective concentration for thecomplete composition. Preferably, the composition will comprise fromabout 10 to about 40 weight percent of the contrast agent and morepreferably from about 20 to about 40 weight percent and even morepreferably about 30 to about 35 weight percent. When the contrast agentis not soluble in the biocompatible solvent, stirring is employed toeffect homogeneity of the resulting suspension. In order to enhanceformation of the suspension, the particle size of the contrast agent ispreferably maintained at about 10 μm or less and more preferably at fromabout 1 to about 5 μm (e.g., an average size of about 2 μm). In onepreferred embodiment, the appropriate particle size of the contrastagent is prepared, for example, by fractionation. In such an embodiment,a water insoluble contrast agent such as tantalum having an averageparticle size of less than about 20 microns is added to an organicliquid such as ethanol (absolute) preferably in a clean environment.Agitation of the resulting suspension followed by settling forapproximately 40 seconds permits the larger particles to settle faster.Removal of the upper portion of the organic liquid followed byseparation of the liquid from the particles results in a reduction ofthe particle size which is confirmed under an optical microscope. Theprocess is optionally repeated until a desired average particle size isreached.

The particular order of addition of components to the biocompatiblesolvent is not critical and stirring of the resulting suspension isconducted as necessary to achieve homogeneity of the composition.Preferably, mixing/stirring of the composition is conducted under ananhydrous atmosphere at ambient pressure. The resulting composition isheat sterilized and then stored preferably in sealed amber bottles orvials until needed.

Each of the polymers recited herein is commercially available but canalso be prepared by methods well known in the art. For example, polymersare typically prepared by conventional techniques such as radical,thermal, UV, gamma irradiation, or electron beam induced polymerizationemploying, as necessary, a polymerization catalyst or polymerizationinitiator to provide for the polymer composition. The specific manner ofpolymerization is not critical and the polymerization techniquesemployed do not form a part of this invention. In order to maintainsolubility in the biocompatible solvent, the polymers described hereinare preferably not cross-linked.

In another particularly preferred embodiment of the nonaqueous solution,the biocompatible polymer composition can be replaced with abiocompatible prepolymer composition containing a biocompatibleprepolymer. In this embodiment, the composition comprises abiocompatible prepolymer, an optional biocompatible water insolublecontrast agent preferably having an average particle size of about 10 μmor less and, optionally, a biocompatible solvent.

The term “biocompatible prepolymer” refers to materials which polymerizein situ to form a polymer and which, in the amounts employed, arenon-toxic, chemically inert, and substantially non-immunogenic when usedinternally in the patient and which are substantially insoluble inphysiologic liquids. Such a composition is introduced into the body as amixture of reactive chemicals and thereafter forms a biocompatiblepolymer within the body. Suitable biocompatible prepolymers include, byway of example, cyanoacrylates, hydroxyethyl methacrylate, siliconprepolymers, and the like. The prepolymer can either be a monomer or areactive oligomer. Preferably, the biocompatible prepolymer is alsonon-inflammatory when employed in situ.

Prepolymer compositions can be prepared by adding sufficient amounts ofthe optional contrast agent to the solution (e.g., liquid prepolymer) toachieve the effective concentration for the complete polymercomposition. Preferably, the prepolymer composition will comprise fromabout 10 to about 40 weight percent of the contrast agent and morepreferably from about 20 to about 40 weight percent and even morepreferably about 30 weight percent. When the contrast agent is notsoluble in the biocompatible prepolymer composition, stirring isemployed to effect homogeneity of the resulting suspension. In order toenhance formation of the suspension, the particle size of the contrastagent is preferably maintained at about 10 μm or less and morepreferably at from about 1 to about 5 μm (e.g., an average size of about2 μm).

When the prepolymer is liquid (as in the case of polyurethanes), the useof a biocompatible solvent is not absolutely necessary but may bepreferred to provide for an appropriate viscosity in the nonaqueoussolution. Preferably, when employed, the biocompatible solvent willcomprise from about 10 to about 50 weight percent of the biocompatibleprepolymer composition based on the total weight of the prepolymercomposition. When a biocompatible solvent is employed, the prepolymericcomposition typically comprises from about 90 to about 50 weight percentof the prepolymer based on the total weight of the composition.

In a particularly preferred embodiment, the prepolymer is cyanoacrylatewhich is preferably employed in the absence of a biocompatible solvent.When so employed, the cyanoacrylate adhesive is selected to have aviscosity of from about 5 to about 20 centipoise at 20° C.

The particular order of addition of components is not critical andstirring of the resulting suspension is conducted as necessary toachieve homogeneity of the composition. Preferably, mixing/stirring ofthe composition is conducted under an anhydrous atmosphere at ambientpressure. The resulting composition is sterilized and then storedpreferably in sealed amber bottles or vials until needed.

Specific embodiments of nonaqueous solutions suitable for use in theapparatus and methods of the invention are described in U.S. Pat. Nos.5,667,767 dated Sep. 16, 1997, 5,580,568 dated Dec. 3, 1996 and5,695,480 dated Dec. 9, 1997 and International Publication Number WO97/45131 having an International Publication Date of Dec. 4, 1997, theentire contents of which are incorporated herein by this reference.

Other suitable implantable materials include any material capable ofbeing delivered through a needle, solutions, suspensions, slurries,biodegradable or nonbiodegradable materials and two part or othermixtures. Exemplary implantable materials include injectable bioglass asdescribed in Walker et al., “Injectable Bioglass as a PotentialSubstitute for Injectable Polytetrafluorethylene Particles”, J. Urol.,148:645-7, 1992, small particle species such as polytetrafluoroethylene(PTFE) particles in glycerine such as Polytef®, biocompatiblecompositions comprising discrete, polymeric and silicone rubber bodiessuch as described in U.S. Pat. Nos. 5,007,940, 5,158,573 and 5,116,387to Berg, biocompatible compositions comprising carbon coated beads suchas disclosed in U.S. Pat. No. 5,451,406 to Lawin, collagen and otherbiodegradable material of the type disclosed in U.S. Pat. No. 4,803,075to Wallace et al., biocompatible materials such as disclosed in U.S.Pat. No. 6,296,607 to Milbocker, U.S. Pat. No. 6,524,327 to Spacek, andU.S. Publication Nos. 2002/0049363 and 2003/0135238 to Milbocker, andother known injectable materials.

A kit 121 for a use in treating a wall forming the upper portion of agastrointestinal tract in a human body in accordance with the method ofthe present invention is shown schematically in FIG. 5. Kit 121 includesa package 122 made from any suitable material such as cardboard orplastic for carrying the contents thereof. An exemplary package 122,shown in FIG. 5, is a box formed from a bottom wall 123, four side walls124 and a top wall 126. A portion of top wall 126 is cut away in FIG. 5to reveal an internal space 127 formed by walls 123, 124 and 126. Thecontents of receptacle or package 122 are disposed in internal space127.

Ablation apparatus 26 is carried by package 122 within internal space127. As discussed above, the ablation apparatus 26 includes elongatemember 51 having an inflatable device 53 and an ablation element 73 onthe distal extremity thereof. Kit 121 further includes injection deviceor needle assembly 96 carried by package 122 within internal space 127.The injection device 96 includes stylet 97 having needle member 98 andoptional sleeve 99. A cap 128 is removably attached to distal endportion 99 b of the sleeve 99 for protecting users against undesirablepunctures by needle 104 during storage and setup.

A reservoir or syringe 112 and a container or vial 131 of theimplantable material referred to above can optionally be included,separately or together, within kit 121. Where vial 131, shown with cap132 in FIG. 5, contains a solution for example of an implant-formingmaterial, luer fitting portion 133 of the syringe 112 is removablycoupleable to cap 132 of the vial 131. The luer fitting portion 133 ofthe syringe 112 is also removably coupleable to fitting 72 offinger-grippable element 71 of injection device 96. Additional optionalcomponents of kit 121 include a second reservoir, such as syringe 136,and a container of a biocompatible solvent such as DMSO in the form ofvial 137. Vial 137 includes a cap 138 and syringe 136 has a luer fittingportion 141 removably coupleable to cap 138 of the vial 137. Kit 121 canoptionally further include a suitable incising element such as guidewire83. A third reservoir or syringe (not shown) and/or a vial of aqueoussolution such as saline solution (not shown) can also be optionallyincluded in kit 121.

To assist in describing the utilization of the devices and practice ofthe method of the present invention, a portion of a mammalian body, inthis case a human body 151, is shown in FIGS. 6-12. Body 151 has aninternal cavity in the form of the passage of the esophagus 152extending through a lower esophageal sphincter 153 to a stomach 154.Such cavity is accessible by a natural body opening in the form of mouth156 and is defined by a wall 157 having a surface 158 which surroundsthe esophagus. Esophagus 152 is part of the gastrointestinal tract ofbody 151 that extends from mouth 156 to an anus (not shown). Theesophageal mucosa 159 serves as the inner layer of the intraluminal wall157 in the esophagus 152. Wall 157 has a plurality of tissue layers,including a muscle layer comprising layer of circular muscle 162extending beneath mucosa layer 159 and layer of longitudinal muscle 163beneath circular muscle 162. The muscle layers 162 and 163 each extendaround the esophagus 152 and the stomach 154. Wall 157 further includesa submucosal layer or submucosa 164 extending between mucosa 159 andmuscle layers 162 and 163. A submucosal space, that is a potentialspace, can be created between submucosa 164 and circular muscle layer162 by the separation of layer 159 from muscle layer 162. In addition,as with any muscle, wall 157 includes an intramuscular potential space,that is a space which can be created intramuscularly by distension andseparation of muscle fibers within a single muscle, such as for exampleseparation or dissection of circular muscle layer 162 from longitudinalmuscle layer 163. Wall 157 has a depth or thickness which includes atleast mucosal layer 159, submucosal layer 164, circular muscle layer 162and longitudinal muscle layer 163. The phreno-esophageal ligament 166and diaphragm 167 extend around the esophagus 152 above the loweresophageal sphincter 153. “In the vicinity of the lower esophagealsphincter,” as that term is used herein, includes at least the lowerthird of the esophagus 152, the squamous columnar junction 168, and thegastric cardia or upper portion of the stomach 154.

Although medical device 21 can be used in any number of procedures, inone preferred procedure the device is introduced into a natural bodyopening to access a vessel in the body such as a passageway or an organ.In a further preferred procedure, device 21 can be utilized to deliverof a material, such as a fluid, solution or composition, to a wall of apassageway within a mammalian body to treat the body and moreparticularly to treat the wall forming the gastrointestinal tract of amammalian body. Exemplary procedures can include the treatment ofgastroesophageal reflux disease as described in part in U.S. Pat. Nos.6,238,335 and 6,251,064, the treatment of the gastrointestinal tract andother cavities in a mammalian body as described in part in U.S. Pat.Nos. 6,251,063 and 6,575,896, the treatment of morbid obesity asdescribed in part in U.S. Pat. Nos. 6,540,789, 6,802,863, 7,044,979 and7,364,591 and the treatment of fecal incontinence as described in partin U.S. Pat. Nos. 6,533,717 and 6,595,910, the entire content of each ofsuch patents being incorporated herein by this reference. In each ofsuch procedures, an implant can be formed in a muscle or other layer ofa wall forming an internal cavity of a mammalian body to reduce thedistensibility of or otherwise treat the tissue of the wall, for examplemuscle in the wall in the vicinity of a sphincter. The exemplaryprocedure utilized for describing the devices and methods of the presentinvention is the treatment of gastroesophageal reflux disease.

In operation and use of medical device 21 having ablation apparatus 26and injection device 96 in the method of the present invention, kit 121is opened and the distal extremity 51 b of elongate member 51 isinserted into side port 46 of probe 22 and slid through the probepassageway 36 so that the dissecting element 54 and ablation element 73are carried by the distal extremity 51 b of the elongate member 51.Balloon 54 and the rounded end 52 of elongate member 51 are preferablyrecessed within the passageway 36. Guidewire 83 is removed from kit 121and wire distal extremity 83 b is slid through finger-grippable element71 into passageway 81 of the elongate member 51 so that the distal tipof the guidewire is disposed proximally of distal opening 82 of thepassageway 81. In this manner, incising element 83 is carried by thedistal extremity 51 b of the elongate member 51. A suitable inflationfluid supply 27, such as a syringe or other suitable reservoir of asaline solution, is fluidly coupled to fitting 72 of finger-grippableelement 71 by means of inlet line 63. Optional pressure monitor or gauge61 and pump 62 can be included in line 63 between supply 27 and fitting72. A radio frequency generator and controller 28 is electricallycoupled to connector 77 of the element 73 and a return electrode 78 iselectrically coupled to the generator 28. Probe 22 is prepared byconnecting light cable 42 to light source 43 and attaching the propereye piece 41 to handle 33. In addition, all other conventionalattachments are applied to probe 22.

During the preparation of the patient, return electrode or ground pad 78is adhered or otherwise affixed to the backside or another suitableexterior location on the patient. After the patient has beenappropriately sedated or anesthetized, probe handle 33 is grasped by thephysician to introduce distal extremity 31 b of probe 22 into mouth 156and advance insertion tube 31 down esophagus 152 to the vicinity of thelower esophageal sphincter 153. Insertion tube 31 has a length so thatwhen distal extremity 31 b is in the vicinity of the tissue beingtreating, in this case in the vicinity lower esophageal sphincter 103,proximal extremity 31 a is outside of body 151.

Under the guidance of optical viewing device 23, the physician movesdistal extremity 31 b of the insertion tube 31 to the appropriatelocation near lower esophageal sphincter 153. Rounded end 52 of ablationapparatus 26 is then advanced distally from passageway 36 towards tissuewall 157 and then guidewire distal extremity 83 b is advanced distallyfrom opening 82 of the ablation apparatus towards the wall 157. In onepreferred procedure, the outer surface 158 of wall 157 is cut or nickedby sharpened tip 86 of the guidewire 83 (see FIG. 8). Guidewire distalextremity 83 b is then retracted into elongate member 51 of the ablationapparatus 26 and rounded end 52 of the ablation apparatus pushed throughsurface 158 into the incision or slit made by the guidewire by thephysician grasping finger-grippable element 71 and moving it towardsside port 46. Rounded end 52 can then be pushed deeper into wall 157 toextend the depth of the incision. The presence of guidewire 83 withinpassageway 81 of the ablation apparatus 26 desirably stiffens theapparatus 26 during such blunt dissection of wall 57. Upon reaching oneof muscle layers 162 and 163, for example, the boundary between circularmuscle layer 162 and longitudinal muscle layer 163, further advancementof distal extremity 51 b of the ablation apparatus 26 causes adissection or separation of the circular muscle layer 162 from thelongitudinal muscle layer 163, as shown in FIG. 9. Although notrequired, it is preferred that distal extremity 51 b of the ablationapparatus 26 be introduced a sufficient distance within wall 157 so thatthe entire length of balloon 54 extends between the layers of tissuewhich are intended to be separated, for example between circular musclelayer 162 and longitudinal muscle layer 163 as shown in FIG. 9, oralternatively between submucosal layer 164 and circular muscle layer162.

It is appreciated that other methods may be utilized for introducingdistal extremity 51 b of the ablation apparatus 26 to a desired locationwithin wall 157. For example, after guidewire 83 has been used asdiscussed above to initially incise tissue wall 157, the guidewire canbe pushed distally further into wall 157 to a desired location, forexample to a location which will permit the desired placement of balloon54 within the wall 157. In another example, guidewire 83 may be utilizedseparately from ablation apparatus 26 and introduced into side port 46and insertion tube passageway 36 without ablation apparatus 26. Thesharpened tip 86 of the guidewire can thereafter penetrate wall 157 anddistal extremity 83 b of the guidewire advanced into the wall to adesired location, such as discussed above. After the guidewire 83 haspenetrated wall 157 to a desired depth, the guidewire 83 then bewithdrawn from probe 22 and ablation apparatus 26, without the guidewire83 therein, inserted into passageway 36 of the probe. The operatingphysician thereafter pushes rounded end 52 of the ablation apparatusinto the incision made by guidewire 83 until balloon 54 is at a desiredlocation within such incision or, in a manner similar to that discussedabove, is pushed further into the wall 157 so as to extend the length ofthe incision within the wall. In such a procedure, ablation apparatus 26would not require optional passageway 81.

Where guidewire 83 is utilized for making an incision in wall 157, thepenetration of the guidewire into wall can be monitored under directvisualization by means of optical viewing device 23 and the depth ofpenetration determined by any suitable means, for example byvisualization through optical device 23 of gradations provided on distalextremity 83 b of the guidewire or by visualization outside body 151 ofthe patient of gradations provided on proximal extremity 83 a of theguidewire. In another approach, a depth stop can be placed on proximalextremity 83 a of the guidewire for limiting distal travel of theguidewire. In yet another approach, the apparatus and process ofmonitoring depth by measuring impedance as disclosed in U.S. patentapplication Ser. No. 11/120,436 filed May 2, 2005 [Attorney Docket No.34347/US/2 (449346-127)], the entire content of which is incorporatedherein by this reference, can be utilized.

Other devices can be used, separately or in combination with ablationapparatus 26, for creating an incision in wall 157 into which balloon 54is disposed. For example, a radio frequency device with a sharpened-tipradio frequency electrode at the distal end thereof can be provided forcreating an incision into which balloon 54 is introduced or rounded end52 of the ablation apparatus 26 disposed for extending the length of theincision.

Once balloon 54 has been properly positioned within the wall 157, thephysician inflates the balloon so as to further dissect tissue withinwall 157 and thus create a cavity or pocket within the wall (see FIG.9). In this regard, the fluid within inflation fluid supply 27 isintroduced through inflation lumen 58 into balloon interior 57 so as tocause the balloon 54 to inflate. Pump 62 or hand pressure can beutilized for urging the inflation fluid into balloon 54. In FIG. 9,balloon 54 has been inflated between circular muscle layer 162 andlongitudinal muscle layer 163 so as to create a cavity or pocket 181formed by an internal surface 182 of muscle layers 162 and 163. The sizeof the inflated balloon 54, and hence the size of cavity 181, can bepredetermined by introducing a known amount of inflation fluid into theballoon. In this manner, cavities of different size can be created byintroducing appropriate predetermined volumes of inflation fluid intothe balloon 54.

The location of cavity 181 within the tissue of wall 157 can bemonitored by optical viewing device 23 to determine if the implant to beformed is at the proper longitudinal and latitudinal location within theesophagus 152 and within the muscle layer of wall 157. In this regard,the inflated balloon 54 causes a bulge 183 to form on the interiorsurface 158 of wall 157. The location of the bulge on wall 157determines the longitudinal and latitudinal location of cavity 181 whilea changed characteristic of surface 158 of the wall 157 at the bulge canindicate in which tissue layer of wall 157 the cavity 181 has beenformed. For example, if surface 158 at the bulge 183 is not discolored,that is it remains the same color as the color of the adjacent portionsof the wall 157, cavity 181 has been formed within the muscle layer ofwall 157. If bulge 183 is discolored, for example under fluoroscopy thecontrast is black or under ultrasound the cavity 181 is black or underoptical the tissue forming the bulge turns from dark grey to dark redand then to brown, then cavity 181 has been formed in submucosa layer164 or the mucosa 158 of the wall 157. As discussed above, it ispreferred that cavity 181 be formed within one or both of muscle layers162 and 163 and preferably between the layers 162 and 163 as shown inFIG. 9.

The location of cavity 181 within the tissue of wall 157, that is thelayer of tissue in the wall in which the cavity is located, canadditionally be determined by monitoring the pressure required toinflate balloon 54. Such pressure monitoring can be accomplished, forexample, by means of pressure monitor 61 which periodically orcontinuously checks the pressure in inlet line 63 and thus the output ofpump 62. In this regard, the pressure required to inflate balloon 54between circular muscle layer 162 and longitudinal muscle layer 163 canbe predetermined through empirical testing involving previous proceduresor cadavers. In a similar manner, the pressures required to inflateballoon 54 at other depths and corresponding locations in wall 157 canbe predetermined. The values read by monitor 61 can be compared by thesepredetermined values during the procedure so as to provide the physicianwith the location of cavity 181 within wall 157 and specifically withinthe plurality of tissue layers of the wall 157.

Internal surfaces 182 of cavity 181 are thereafter ablated by thephysician. In this regard, radio frequency energy provided by radiofrequency generator and controller 28 is supplied to ablation apparatus26, and specifically, to ablation element 73 provided on the distalextremity of the ablation apparatus. Electrode 74 is thus energized andradio frequency energy therefrom travels through the conductiveinflation fluid within balloon 54 and travels with such fluid as itweeps out through pores 79 in the balloon. The radio frequency energytravels from balloon 54 to return electrode 78 in a conventional mannerso as to ablate the tissue of the wall 157 in the vicinity of and morespecifically surrounding the balloon 54. The amount of fluid seepagethrough pores 79 is generally very small and thus does not significantlyaffect the pressure required by pump 62 or other inflation device toinflate balloon 54. A layer of ablated tissue 186, also referred toherein as a lesion 186, so formed by ablation element 73 is shown inFIG. 10. The weeping fluid from balloon 54 serves to moisten the tissuesurrounding the balloon and thus permit the ablation lesion to expandoutward and form a deep lesion. In one preferred procedure, the amountof watts supplied by the generator 28 can be based on one or both oftime and impedance feedback.

When it is desired to create a deeper lesion surrounding cavity 181, theinflation fluid can optionally be recirculated through inlet line 63 andinflation lumen 58 to interior 57 of the balloon 54 and back out of theballoon through return lumen 59 and return line 64. As the salinesolution or other inflation fluid recirculates through inflation fluidsupply 27, or any other conventional cooling mechanism, the solution orother fluid can be cooled so that a predetermined and desired fluidtemperature is maintained within balloon 54 during the ablation process.Such cooled fluid serves to cool the tissue surrounding cavity 181 so asto prevent tissue necrosis and thereby increase the depth of the lesioncreated in the tissue adjacent the balloon 54 by ablation element 73.

Upon completion of the ablation process, balloon 54 is deflated and theablation apparatus 26 removed from probe 22. The ablation of theinternal surfaces 182 of cavity 181, and the resulting lesion 186 formedthereby, inhibits the collapse of cavity 181 upon the deflation andremoval of balloon 54. In one embodiment, injection device 96 isinserted into the probe by introducing respective distal extremities 98b and 96 b of the needle member 98 and sleeve 99 into side port 46 andpassageway 36. Needle member 98 and sleeve 99 are each moveable betweena first position in which distal extremities or end portions 98 b and 99b are each retracted within insertion tube 31, and thus recessed withinpassageway 36 of the insertion tube, and a second position in which thedistal end portions 98 b and 99 b extend distally beyond the distal endof insertion tube 31. The needle member 98 and sleeve 99 each havesufficient lengths so that the physician can extend them distally fromthe end of insertion tube 31 a sufficient distance, should that bedesired, by use of respective fluid connector 107 and grip 108. Supply27 is filled with an appropriate material in preparation of theprocedure and coupled to the proximal extremity of needle member 98 bymeans of fluid connector 107.

The physician causes the sharpened tip of needle 104 to penetrate wall157 in the vicinity of bulge 183 and thereafter moves the needle member98 distally a sufficient distance so that the distal end of the needle104 enters cavity 181. The field of view of optical viewing device 23facilitates observation of the penetration of wall 157 by needle member98. The physician then causes an appropriate amount of the implantableor injectable material to be introduced through needle 104 and into wall157 to form at least one implant 187 in the wall. Preferably a pluralityof implants 187 are formed in wall 157, and such a plurality of implantscan be arranged in any suitable configuration, such as for example anyof the configuration of implants disclosed in U.S. Pat. No. 6,251,063.The injectable material can be deposited into any or all of the layersof wall 157, including between any of such layers. The implant can be ofany suitable shape, for example an arcuate implant which extends arounda portion or all of the wall as disclosed in U.S. Pat. No. 6,251,064,the entire content of which is incorporated herein by this reference.The implants can serve to augment the wall, bulk the wall, reduce thedispensability of muscle layers 162 and/or 163 of the wall, or serve anyother purpose for treating the wall. When the ailment being treated isgastroesophageal reflux disease, the implant can serve to increase thecompetency of the lower esophageal sphincter 153.

It is appreciated that a suitable injection device, such as injectiondevice 96, can be utilized for forming at least one implant 187 in thewall without the use of probe 22 and be within the scope of the presentinvention. In this regard, the injection device is introduced into thepatient directly, that is not within probe 22, and extended to thevicinity of treatment for creation of the at least one implant.

The ablation of internal surfaces 182 of the wall 157, and the creationof lesion 186 adjacent cavity 181, serves to create a sealed capsule forimplant 187 and minimizes or inhibits migration of the implant fromcavity 181 into the adjoining tissue. Such a sealed capsule, incombination with introduction of a predetermined amount of implantablematerial into cavity 181, can advantageously provide an implant 187 of apredetermined volume and thus a procedure for the repeatable creation ofappropriately sized implants. It is appreciated that the size and shapeof balloon 54, along with the amount of inflation fluid introduced intothe balloon 54 during inflation, can be adjusted to vary the size andshape of cavity 181 and thus the size and shape of the resulting implant187. In this regard, balloon 54 can be spherical, round, semicircular orany other suitable geometric shape.

In another embodiment and procedure of the invention, treatment device21 does not include an implant-forming apparatus such as injectiondevice 96. In one such embodiment and procedure, no implants are formedor disposed in cavity 181 after the ablation of internal surfaces 182 ofthe cavity 181 and the creation of lesion 186. Instead, the ablatedtissue of the cavity wall and resulting lesion 186 can serve to remodelthe tissue structures, reduce the distensibility of the targeted muscleor other tissue of the wall or otherwise treat the tissue and affectedarea of the mammalian body.

Other embodiments of ablation element 73 can be provided and be withinthe scope of the present invention. For example, the ablation element 73can be a bipolar device. FIG. 2 includes a second or return electrode191, drawn in dashed lines, to illustrate one embodiment of such abipolar ablation element 73. The return electrode 191 shown in FIG. 2 issubstantially similar to first or active electrode 74, and is located ondistal extremity 51 b of the elongate member 51 within interior 57 ofballoon 54 a distance spaced proximally of the active electrodes 74. Anadditional lead (not shown), which can be substantially similar to lead75, is electrically coupled to the return electrode 191 and extendsthrough elongate member 51 to an additional connector (not shown), whichcan be substantially similar to connector 76. Such additional connectoris electrically coupled in any suitable manner, for example by a cable(not shown) which can be similar to cable 77, to radio frequencygenerator and controller 28. When medical device 21 is such a bipolardevice, external return electrode 78 is not required.

Other suitable embodiments of the ablation apparatus of the presentinvention can be provided. Ablation apparatus 201 illustrated in FIGS.13 and 14 is substantially similar to ablation apparatus 26 and likereference numerals have been used herein to described like components ofablation apparatus 26 and 201. An elongate member 202, substantiallysimilar to elongate member 51, is included within ablation apparatus 201and has a proximal extremity (not shown) and a distal extremity 203. Theapparatus 201 further includes a rounded end 204 substantially similarto rounded end 56 of the ablation apparatus 26. Ablation apparatus 201includes a balloon 54 formed from a balloon body 56 having proximal anddistal end portions 56 a and 56 b. An inflation lumen 58 is provided inelongate member 202 for supplying an inflation fluid to balloon 54, andan optional return lumen 59 and passageway 81 can be provided in theelongate member 202 (See FIG. 14). Balloon body 56 is preferably formedwithout pores 79.

An ablation element 211 is carried by distal extremity 203 of theelongate member 202 and includes at least one active electrode andpreferably and a plurality of active electrodes 212 carried by externalsurface 213 of balloon body 56. In the preferred embodiment shown inFIGS. 13 and 14, the plurality of active electrodes 212 include aplurality of longitudinally-extending strips or conductive pathways 212which each extend from the proximal extremity to the distal extremity ofthe balloon 54 in circumferentially spaced-apart positions. Ablationelement 211 further includes at least one and preferably a plurality ofconductive pathways or return electrodes 216 provided on externalsurface 213 of the balloon 54. The return electrodes are preferablysimilar in construction to active electrodes 212 and thus extend fromthe proximal extremity to the distal extremity of the balloon 54 incircumferentially spaced-apart positions. A return electrode 216 ispreferably spaced between each adjacent pair of active electrodes 212,with the spacing between each adjacent active electrode and returnelectrode being approximately equal. The active and return electrodes212 and 216 can be formed in any suitable manner, for example suchelectrodes can each be formed from a wire or a machined shape, or from amaterial such as a conductive ink, metallic particles, conductivepolymers or a stamp formed on the outer surface 213 of the balloon body56.

At least one first or active lead 218 extends through elongate member202 for providing electrically energy, preferably in the form of radiofrequency energy, to the active electrodes 212, and at least one secondor return lead 219 extends through the elongate member 202 for receivingenergy from the return electrodes 216. Each of the leads 218 and 219 iscoupled at its distal end to their respective electrode or electrodesand at its proximal end to a connector, for example a connector similarto connector 76, for permitting electrical communication between theactive and return electrodes and radio frequency generator andcontroller 28. Active and return leads 218 and 219 can be formed in anysuitable manner. For example, one of the leads, such as active lead 218,can be in the form of a first coating 221 which is annular in crosssection, as shown in FIG. 14, and extends from the proximal extremity tothe distal extremity 203 of elongate member 202. A nonconductive orinsulative coating 222 is disposed around substantially the entirelength of the first conductive coating 221. The second lead, such asreturn lead 219, can be formed from a similar second conductive coating223 disposed around first nonconductive coating 222 from the proximalextremity to the distal extremity 203 of the elongate member 202. Asecond nonconductive or insulative coating 224 extends aroundsubstantially the entire length of the second conductive coating 223.First and second conductive coatings 221 and 223 are made from anysuitable material or materials such as a metal or a polymer andpreferably gold, silver, platinum, iron oxide particles and otherconductive elements and more preferably gold or a conductive polymer,and can be formed in any suitable manner such as dip coating, spraying,plating or vapor deposition. First and second insulative coatings 222and 224 can be made from any suitable material or materials such as athermoplastic or a thermoplastic elastomer such aspolytetrafluoroethylene, polyurethane, silicone and other non-conductiveelements and preferably polyurethane, and can be formed in any suitablemanner such as blow molding, injection molding, shrink wrapping ortubing, dip coating, spraying and extrusion.

Ablation apparatus 201 is operated with probe 22 in substantially thesame manner as discussed above with respect to ablation apparatus 26 toform an implant in wall 157 that is less susceptible to migration. Inthis regard, a cavity 181 is formed in the wall 157 by dissectingballoon 54. The one or more active electrodes 212 of the ablationapparatus are energized with radio frequency energy supplied bygenerator and controller 28 to create a lesion 186 around the cavity. Animplantable material is introduced into the cavity 181 with injectiondevice 96 to form an implant in wall 157.

Bipolar ablation apparatus 201 can be simplified to provide a monopolarablation apparatus for use with an external indifferent or returnelectrode such as return electrode 78 discussed above. Such a monopolarablation apparatus does not include return electrodes 216 on balloon 54and, instead, merely includes a plurality of circumferentiallyspaced-apart active electrodes 212 on external surface 213 of theballoon body 56. Similarly, the return lead 219 formed from secondconductive coating 223, and the related second nonconductive coating224, are not required in such a monopolar ablation apparatus. It isappreciated, however, that ablation apparatus 201 can also be operatedin a monopolar mode by supplying radio frequency energy to both activeand return leads 118 and 119 so that both sets of electrodes 212 and 216serve as active electrodes.

The bipolar apparatus of the invention, for example bipolar ablationelement 73 with return electrode 191 and bipolar apparatus 201, areadvantageous because they typically can eliminate the need for agrounding pad or other return electrode external of the body. Suchelimination can reduce the cost and steps of a procedure utilizing suchan apparatus, thus providing a simplified procedure. In addition,locating a return or inactive electrode in close proximity to the activeelectrode, such as in a bipolar device, can serve to better concentrateradio frequency energy in the targeted tissue and thus increase theefficacy of a procedure employing such bipolar or other active andinactive electrodes in such close proximity to each other in comparisonto a related monopolar procedure.

A further embodiment of an ablation apparatus of the present inventionsis shown in FIG. 15. Ablation apparatus 231 therein is substantiallysimilar to ablation apparatus 26 and like reference numerals have beenused to describe like components of ablation apparatus 26 and 231. Anelongate member 51, having a balloon 54 at its distal extremity, isincluded within ablation apparatus 231. An inflation lumen 58 (notshown) extends through the elongate member 51 and optional return lumen29 and passageway 81 (not shown) can also extend through the elongatemember 51. Balloon body 56 is preferably formed without pores 79.

An ablation element 232 is included within the ablation apparatus 231and preferably includes a single electrode 233 formed on at least aportion of, and preferably the entire external surface of, balloon body56 (see FIG. 15). Electrode 233 is formed in any suitable manner and ispreferably formed from a conductive coating 234 made from any suitablematerial or materials such as a metal or a polymer and preferably gold,silver, platinum, iron oxide particles and other conductive elements andmore preferably gold or a conductive polymer, and can be formed in anysuitable manner such as dip coating, spraying, plating or vapordeposition. Active electrode 233 is electrically coupled to radiofrequency generator and controller 28 by any suitable means such as alead 75 (not shown), or alternatively lead 218 of ablation apparatus 201(not shown), extending through the elongate member 51 of ablationapparatus 231.

An ablation apparatus 241 having similarities to ablation apparatus 231is shown in FIG. 16, and like reference numerals have been used todescribe like components of ablation apparatus 231 and 241. Balloon body56 of the ablation apparatus 241 does not include pores 79. An ablationelement 242 having a single active electrode 243 is included withinablation apparatus 241. Electrode 243 is formed from a conductivecoating 244 which is substantially similar to the conductive coating 234of ablation apparatus 231 but extends over only a portion of balloonbody 56. Specifically, conductive coating 244 extends around thecircumference of the balloon 54.

Ablation apparatus 231 and 241 can be operated with probe 22, preferablyin a monopolar operation, in substantially the same manner as discussedabove with respect to ablation apparatus 26 but without the weeping of aconductive fluid from the outer surface of balloon body 56. After acavity 181 is formed in the wall 157 by dissecting balloon 56, theconductive coating of such apparatus is energized with radio frequencyenergy to ablate internal surfaces 182 forming such cavity 181.

In another procedure of the invention, an implant formed by one or moreconductive beads or other bodies is created in cavity 181 formed by wall157. The conductive beads or bodies can be introduced into wall 157 bymeans of a tubular needle assembly or any other suitable means, andutilized to create cavity 181 or introduced into the cavity aftercreation of the cavity. Radio frequency energy can be supplied to suchconductive beads or bodies, for example by a conductive lead or bysaline or another conductive liquid in each case coupled directly orindirectly to such conductive beads or bodies, to ablate the wall 157around cavity 181 and form a lesion 186 in the wall. Such conductivebeads or bodies can be of any suitable type and formed from any suitablematerial such as metal. Where biocompatible beads or bodies are soutilized, they can remain in cavity 181 and serve as an implant fortreating the tissue of the wall in the manner discussed above.Alternatively, the beads or bodies can be removed from cavity 181 in anysuitable manner after tissue ablation, for example by incising the wallto access the cavity 181 or by introducing a tubular removal member intothe cavity, and lesion 186 can serve to treat the tissue of the wall inthe manner discussed above.

As can be seen from the foregoing, a method and apparatus have beenprovided for forming implants of a predetermined size at a desiredlocation in the tissue of a mammalian body. The method and apparatus caninhibit migration of the implants within the tissue.

1. A method for treating a mammalian body having tissue comprisingcreating a cavity in the tissue formed by an internal surface of thetissue, ablating the internal surface and introducing an implant-formingmaterial into the cavity to create an implant in the tissue whereby theablation of the internal surface inhibits migration of the implant. 2.The method of claim 1 wherein the creating step includes dissecting thetissue.
 3. The method of claim 2 wherein the dissecting step includesinflating a balloon in the tissue.
 4. The method of claim 3 wherein theablating step includes utilizing the balloon to ablate the tissue. 5.The method of claim 4 wherein the inflating step includes inflating theballoon with a conductive material and the ablating step includesweeping the conductive material from the balloon.
 6. The method of claim5 wherein the ablating step includes energizing an electrode within theballoon to couple radio frequency energy to the conductive material. 7.The method of claim 4 wherein the ablating step includes energizingconductive pathways on a surface of the balloon.
 8. The method of claim4 wherein the ablating step includes energizing a conductive coating ona surface of the balloon.
 9. The method of claim 1 wherein the creatingstep includes providing a catheter having a distal extremity andintroducing the distal extremity into tissue of a wall of the bodyforming a natural body cavity in the body.
 10. The method of claim 9wherein the creating step includes introducing the distal extremity intoa natural body opening to access the natural body cavity.
 11. The methodof claim 9 wherein the creating step includes providing an incisingelement on the distal extremity of the catheter and incising the tissuewith the incising element.
 12. The method of claim 11 wherein thecreating step includes providing a lumen within the catheter whichextends to and opens at the distal extremity of the catheter and slidingthe incising element through the lumen to the distal extremity of thecatheter.
 13. The method of claim 9 wherein the creating step includesproviding a balloon on the distal extremity of the catheter andinflating the balloon in the tissue.
 14. A method for treating amammalian body having a wall formed by a plurality of tissue layerscomprising introducing a balloon into the wall, inflating the balloonwith a fluid having a pressure and measuring the pressure of the fluidso as to determine in which of the plurality of layers the balloon isdisposed.
 15. The method of claim 14 wherein the measuring step includescomparing the measured pressure to a plurality of predeterminedpressures corresponding respectively to the plurality of tissue layers.16. The method of claim 14 further comprising deflating the balloon toprovide a cavity in the wall.
 17. The method of claim 16 furthercomprising forming an implant in the cavity.
 18. The method of claim 14further comprising ablating the wall in the vicinity of the balloon. 19.A method for treating a mammalian body having a wall having a surfaceand formed by a plurality of tissue layers comprising introducing aballoon into the wall, inflating the balloon whereby a bulge is formedon the surface of the wall which changes a characteristic of the surfaceof the wall and observing the changed characteristic to determine inwhich of the plurality of layers the balloon is disposed.
 20. The methodof claim 19 wherein the changed characteristic is selected from thegroup consisting of color of the surface under fluoroscopy, color of thesurface under ultrasound and color of the surface under opticalvisualization.
 21. The method of claim 19 further comprising deflatingthe balloon to provide a cavity in the wall.
 22. The method of claim 21further comprising forming an implant in the cavity.
 23. The method ofclaim 19 further comprising ablating the wall in the vicinity of theballoon.
 24. A method for treating a mammalian body having tissuecomprising creating a cavity in the tissue formed by an internal surfaceof the tissue and ablating the internal surface of the cavity to treatthe tissue.
 25. The method of claim 24 wherein the creating stepincludes inflating a balloon in the tissue.
 26. The method of claim 25wherein the ablating step includes utilizing the balloon to ablate thetissue.
 27. The method of claim 24 wherein the creating step includesproviding a catheter having a distal extremity and introducing thedistal extremity into tissue of a wall of the body forming a naturalbody cavity in the body.
 28. The method of claim 27 wherein the creatingstep includes introducing the distal extremity into a natural bodyopening to access the natural body cavity
 29. The method of claim 24wherein the creating step includes introducing a plurality of conductivebodies into the tissue.
 30. The method of claim 29 wherein the ablatingstep includes supplying radio frequency energy to the conductive bodies.31. The method of claim 30 further comprising removing the conductivebodies from the tissue after the ablating step.
 32. An apparatus forcreating a cavity in tissue formed by an internal surface of the tissuecomprising a flexible elongate member having proximal and distalextremities, an expandable-collapsible body carried by the distalextremity of the flexible elongate member and capable of expanding inthe tissue to form the cavity, an ablation element carried by the distalextremity of the flexible elongate member and coupled to theexpandable-collapsible body for ablating the internal surface of thetissue forming the cavity, and an incising element carried by the distalextremity of the flexible elongate member for introducing theexpandable-collapsible body into the tissue.
 33. The apparatus of claim32 wherein the expandable-collapsible body is provided with a pluralityof pores and the ablation element includes an electrode disposed on theelongate member within the expandable-collapsible body.
 34. Theapparatus of claim 32 wherein the expandable-collapsible body has anexterior surface and the ablation element includes conductive pathsformed on the external surface of the expandable-collapsible body. 35.The apparatus of claim 32 wherein the expandable-collapsible body has anexterior surface and the ablation element includes a conductive coatingprovided on the external surface of the expandable-collapsible body. 36.The apparatus of claim 32 wherein the flexible elongate member has alumen extending to and opening at the distal extremity of the elongatemember and the incising element includes a wire slidably disposed in thelumen, the wire having a sharp distal end slidable to an extendedposition beyond the distal extremity of the flexible elongate member.37. A kit for creating a cavity in tissue formed by an internal surfaceof the tissue and for introducing an implant-forming material into thecavity comprising a package, a first elongate member provided within thepackage and having proximal and distal extremities, anexpandable-collapsible body carried by the distal extremity of the firstelongate member and capable of expanding in the tissue to form thecavity, an ablation element carried by the distal extremity of the firstelongate member and coupled to the expandable-collapsible body forablating the internal surface of the tissue forming the cavity and asecond elongate member provided within the package and having proximaland distal extremities and a lumen extending from the proximal extremityto the distal extremity of the second elongate member whereby animplant-forming material can be introduced into the lumen at theproximal extremity of the second elongate member for delivering theimplant-forming material to the cavity in the tissue.
 38. The kit ofclaim 37 further comprising an incising element carried by the distalextremity of the first elongate member.
 39. The kit of claim 37 whereinthe second elongate member includes an elongate sleeve having a lumenextending longitudinally therethrough and a needle member slidablydisposed in the lumen of the elongate sleeve.
 40. The kit of claim 37further comprising a container of the implant-forming material providedwithin the package.
 41. The kit of claim 40 further comprising acontainer of a biocompatible solvent provided within the package. 42.The kit of claim 40 further comprising a syringe for introducing theimplant-forming material into the lumen of the second elongate member.43. The kit of claim 37 wherein the implant-forming material is anonaqueous solution, whereby a nonbiodegradable solid is formed in thecavity from the nonaqueous solution.
 44. The kit of claim 37 furthercomprising an incising element provided within the package forfacilitating entry of the expandable-collapsible body into the tissue.45. The kit of claim 44 wherein the incising element is a guidewire.